Proliferating cell nuclear antigen expression and the progression of cervical intraepithelial neoplasia

Cell proliferation is an important biological aspect of a tumor cell population which can affect clinical outcome. In addition to other well established clinical and histopathological prognostic criteria? cell kinetic data have significant predictive value. This study evaluates the proliferative activity of benign, premalignant and malignant cervical tissue by analyzing the expression of the proliferating cell nuclear antigen (PCNA). PCNA is a 36 kD nuclear protein associated with the cell cycle and is directly involved in DNA synthesis during cell proliferation. A total of 122 subjects were included in the study. This included 30 benign tissue samples, 30 low grade lesions (CIN 1), 30 high grade lesions (CIN 2/3) and 32 invasive squamous carcinomas. There was significant difference in PCNA index between benign and high grade lesions as well as benign and invasive cancer. The percentage of PCNA positive cells were significantly higher in invasive carcinoma when compared with non malignant lesions. Moreover, there was also good correlation between increasing histological abnormality and PCNA expression. These results suggest that cell proliferation index as detected by PCNA expression may be useful in the evaluation of alterations in cell kinetics of various grades of cervical lesions. Such data could also possibly help explain the biological behaviour of these lesions and be useful in planning of radiotherapy for invasive cervical cancer.     

A study of dose distribution patterns from cobalt-60 and Varian Clinac-4 beams.

Dose distribution patterns of 4 MV x-rays from a Varian Clinac 4 linear accelerator are compared with those from a 60Co teletherapy machine. Field flatteners of lead and depleted uranium were used. Dose distribution maps display the off-axis high dose or "horns" with lead filters and circular dose distribution patterns. The uranium field flattener clearly "clipped the horns" and eliminated circular dose distribution patterns with larger fields.     

Effects of smoking on health care costs

Smoking is the leading preventable cause of death in the United States. The US Centers for Disease Control and Prevention (CDC) estimate that smoking kills approximately 419,000 people in the United States each year. Cigarette smoking is the nation's leading cause of premature mortality, and is responsible for one-third of all deaths among working-age Americans. Smoking cigarettes is both psychologically and physiologically addictive. Smoking is an important risk factor for cardiovascular diseases, especially coronary artery disease, stroke, carcinoma of the lung, chronic bronchitis, chronic obstructive pulmonary disease, and emphysema. It also increases the risk for peripheral vascular disease and is associated with cancers of the larynx, oral cavity, esophagus, pancreas, and urinary bladder. Smoking by pregnant women can cause adverse health effects on their babies, like low birth weight and preterm delivery; increases the risk of miscarriage; and has also been found to be an important cause of sudden infant death syndrome. Careless smoking also can cause severe burn injuries and death. Many of these adverse effects of smoking occur in "second-hand" smokers.     

Radiation therapy induced changes in apoptosis and its major regulatory proteins, Bcl-2, Bcl-XL, and Bax, in locally advanced invasive squamous cell carcinoma of the cervix.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for cancer induces cell death by apoptosis. The major apoptotic regulatory molecules include Bcl-2, Bcl-XL (antiapoptotic), and Bax (proapoptotic) proteins. Invasive squamous cell carcinoma of the cervix is mainly treated by radiation, and hence our aim was to evaluate the changes induced by RT in the apoptotic index (AI) and to correlate this to the levels of the major pro- and antiapoptotic molecules. MATERIALS AND METHODS: Paired biopsies were obtained in 30 cases of invasive carcinoma cervix before and after 10 Gy RT. The TUNEL assay was performed to detect apoptotic nuclei and Bcl-2, Bcl-XL, and Bax proteins detected by immunohistochemistry (IHC). Statistical analysis was performed using the Spearman rank correlation coefficient test. RESULTS: Following RT, there was a significant increase in the mean AI [2.25 (+/-2.28) in post-RT vs 0.90 (+/-0.53) in the pre-RT group]. Bax, a major proapoptotic protein, was significantly increased following RT (P < 0.05), whereas the antiapoptotic Bcl-XL showed a significant decrease (P = 0.006). There was no significant change in Bcl-2 expression. The Bcl-2 and Bax IHC scores and the Bcl-2/Bax ratio did not correlate with AI in the 2 groups. There was an inverse correlation of Bcl-XL to AI in the pre-RT group (P = 0.003) but not in the post-RT group. CONCLUSIONS: RT for invasive squamous cell carcinoma of cervix results in increased apoptotic cell death with the up-regulation of Bax, a proapoptotic protein, and the down-regulation of Bcl-XL, an antiapoptotic protein, without any significant change in the levels of Bcl-2.     

Gunshot injuries of the popliteal artery

BACKGROUND: Guidelines for the management of popliteal artery trauma emanate mainly from military experience. This study was undertaken to describe the management of popliteal injuries in a civilian vascular surgical unit with a large trauma workload. METHODS: A retrospective review of records of patients treated between 1983 and 1997 was undertaken. RESULTS: Some 117 popliteal artery gunshot injuries were treated (83 low velocity, 16 high velocity, 18 shotgun). Associated fractures occurred in 44 patients and 40 had popliteal vein injuries. Treatment of the arterial injury included vein graft interposition in 71, primary reanastomosis in 19, prosthetic graft interposition in four, lateral suture in one, vein patch in one and ligation in one patient; 84 fasciotomies were performed. No perioperative deaths occurred. There were 20 primary and 14 secondary amputations. Factors associated with amputation were high-velocity injuries, delay in revascularization in excess of 7 h, arterial transection, associated fracture, and compartment syndrome or muscle infarction. CONCLUSION: Civilian popliteal gunshot injuries are attended by a high amputation rate. Prompt resuscitation and revascularization appear to be the only correctable factors that may improve limb salvage rates.     

Randomized phase II trial of three schedules of pemetrexed and gemcitabine as front-line therapy for advanced non-small-cell lung cancer.

PURPOSE: A randomized three-arm phase II study was undertaken to evaluate the optimum administration schedule of pemetrexed and gemcitabine in chemotherapy-na?ve patients with non-small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to three schedules of pemetrexed 500 mg/m2 plus gemcitabine 1,250 mg/m2, separated by a 90-minute interval, on a 21-day cycle as follows: schedule A, pemetrexed followed by gemcitabine on day 1 and gemcitabine on day 8; schedule B, gemcitabine followed by pemetrexed on day 1 and gemcitabine on day 8; and schedule C, gemcitabine on day 1 and pemetrexed followed by gemcitabine on day 8. RESULTS: One hundred fifty-two eligible patients (schedule A, n = 59; schedule B, n = 31, and schedule C, n = 62) received a median of five (schedule A), two (schedule B), and four (schedule C) treatment cycles. Overall, 66% of patients experienced grade 3 or 4 neutropenia. Common grade 3 and 4 nonhematologic toxicities were dyspnea (11%), fatigue (16%), and transaminase elevation (9%). Schedule A seemed less toxic compared with schedule C (grade 3 or 4 events: 86% v 94%, respectively; P = .19; grade 4 events: 39% v 48%, respectively; P = .30). Schedule B was closed at interim analysis for inferior efficacy. Schedule A, with a confirmed response rate of 31% (95% CI, 20% to 45%), met the protocol-defined efficacy criteria, whereas schedule C, with a confirmed response rate of 16.1% (95% CI, 11% to 34%), did not. Median survival time and time to progression were 11.4 and 4.4 months, respectively, with no observable difference between the arms. CONCLUSION: Pemetrexed and gemcitabine administered as outlined for schedule A met the protocol-defined efficacy criteria, was less toxic compared with the other treatment schedules, and should be further evaluated.     

Peripheral polyneuropathy and acute psychosis from chronic nitrous oxide poisoning: A case report with literature review

Rationale:Nitrous oxide (NO) is a commonly used drug in medical practice, restoration, and the automobile industry. Recreational abuse is an emerging public health problem owing to its accessibility and drug properties.Patient concerns:A 25-year-old male was hospitalized with acute psychosis and lower-extremity sensorimotor proprioceptive ataxia due to nitrous oxide abuse.Diagnosis:Laboratory studies confirmed a vitamin B12 deficiency. Magnetic resonance imaging of the spinal cord showed normal findings. Electrophysiological testing confirmed length-dependent sensorimotor polyneuropathy, with a predominant motor component and axonal degeneration.Intervention and outcomes:Abstinence from toxic substances was suggested, and vitamin B12 substitution was introduced. The patient was lost to follow up.Lessons:Nitrous oxide toxicity is multisystemic and is thought to result from vitamin B12 inactivation. Recent case reports postulated direct paranodal lesions resulting from nitrous oxide consumption. Neurological, neuropsychiatric, and hematological toxicities are among those explored in this case report. Correction of the functional vitamin B12 status and nitrous oxide abstinence are essential in the treatment process.